Midlife smoking continues to be a problem in Australia, with substantial personal, social, and financial costs. Yet the specific characteristics and needs of this group have been largely overlooked. Here we review the literature for the purposes of (1) profiling the characteristics of midlife smokers and (2) assessing the effectiveness of interventions for this group. This review shows midlife smokers differ from younger smokers in important ways: they underestimate the costs of smoking and overestimate the benefits, and are less confident in their ability to quit. The few studies investigating age-tailored interventions have shown these to be effective in reducing midlife smoking. Still, research in this area is limited, with only one study conducted during the past decade that investigated smoking interventions for those in midlife. Clearly there is a need for smoking cessation interventions for midlife smokers that are tailored to the specific beliefs and needs of this unique group. Future research should focus on establishing the best methods for interventions for those individuals who are resistant to earlier interventions and still continue smoking into midlife. Interventions may benefit from incorporating recent evidence about the less obvious costs associated with midlife smoking, including later-life neurological disease.